A cohort of 1,517 former beryllium workers from two facilities in Eastern Pennsylvania has had medical testing and characterization of their exposure. Medical testing has consisted of blood lymphocyte proliferative transformation (LPT), spirometry and a chest x-ray interpreted by a panel of three "B" readers. Beryllium sensitization has been confirmed by a second positive LPT and chronic beryllium disease by lung biopsy and LPT testing of lavage fluid. As part of the medical testing, which has already been performed, whole blood was collected and frozen and a separate consent form to allow for future genetic testing was obtained from participants. Coincidental with the medical testing a detailed exposure assessment for each participant was constructed using all previous air sampling data, review of process and engineering changes over time and interviews with long term workers. Using a 3 to 1 case-control match this proposal will fund genetic testing of individuals with either beryllium sensitization or chronic beryllium disease. This proposal will allow study of the genetic/exposure interaction of a large well characterized group of individuals who all had beryllium exposure and who have a high rate of beryllium sensitization or chronic disease yet only 11.0% of the cohort has developed these changes. The results of this study will help to elucidate the underlying mechanism of beryllium sensitization and chronic disease.